title: Variants in TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3 interact to confer risk of systemic lupus erythematosus in Chinese population.
abstract: Our previous genome-wide association studies on SLE have identified several susceptibility genes involved in NF-κB signaling pathway, including TNFSF4, TNFAIP3, TNIP1, BLK, SLC15A4 and UBE2L3. The aim of this study is to investigate the association model (additive, dominant, recessive) of these genes and search for possible gene-gene interactions between them. In this study, we explored the association model of these six genes and search for possible gene-gene interactions based on identified single-nucleotide polymorphisms (SNPs) among them by using logistic regression analysis in the combined sample of 4,199 cases and 8,255 controls. The most significant association evidence was observed under recessive model for all of these SNPs. Besides, significant interactions between these SNPs were observed in this study: the TNFSF4 and TNIP1 SNPs (P adjusted = 1.68E-10), the TNFSF4 and SLC15A4 SNPs (P adjusted = 3.55E-08), the TNFSF4 and UBE2L3 SNPs (P adjusted = 8.74E-13), the TNIP1 and BLK SNPs (P adjusted = 9.45E-10), the TNIP1 and UBE2L3 SNPs (P adjusted = 8.25E-11), the TNFAIP3 and UBE2L3 SNPs (P adjusted = 3.06E-14) and the BLK and SLC15A4 SNPs (P adjusted = 4.51E-12). These results may contribute to our understanding of SLE genetic interactions and account for the additional risk of certain patients to develop SLE.
authors.affiliation: Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, Hefei, Anhui, China.
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Zuo
authors.forename: Yu-Jun
authors.initials: YJ
authors.lastname: Sheng
authors.forename: Su-Juan
authors.initials: SJ
authors.lastname: Hu
authors.forename: Jin-Ping
authors.initials: JP
authors.lastname: Gao
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Hua-Yang
authors.initials: HY
authors.lastname: Tang
authors.forename: Xian-Fa
authors.initials: XF
authors.lastname: Tang
authors.forename: Hui
authors.initials: H
authors.lastname: Cheng
authors.forename: Xian-Yong
authors.initials: XY
authors.lastname: Yin
authors.forename: Lei-Lei
authors.initials: LL
authors.lastname: Wen
authors.forename: Liang-Dan
authors.initials: LD
authors.lastname: Sun
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D002352:Carrier Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D016015:Logistic Models; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D053278:OX40 Ligand / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics*; D055815:Young Adult; D019061:src-Family Kinases / Q000235:genetics*
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D053278:OX40 Ligand; C491359:SLC15A4 protein, human; C089251:TNFSF4 protein, human; C117046:TNIP1 protein, human; C079437:UBE2L3 protein, human; D044763:Ubiquitin-Conjugating Enzymes; C584409:BLK protein, human; D019061:src-Family Kinases; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3